QSAR Studies of N-(2-Aminophenyl)-Benzamide derivatives as Histone deacetylase2 Inhibitors

Histone deacetylase 2 is a promising target for drug intervention and its inhibitors are useful in treating cancer. QSAR (2D and 3D) studies were performed on a series of N-(2-Aminophenyl)-Benzamide derivatives using Cerius2 software (accelrys). QSAR study performed on 25 analogues of which 21 were used in the training set and the rest 4 considered for the test set. 2DQSAR study performed using Partial least squares (PLS), Genetic function approximation (GFA), Genetic partial least squares (G/PLS). Among these three methods GFA method came out with good correlation coefficient r 0.794, cross-validated coefficient rCV 0.634 and rpred of 0.6343. 3D-QSAR studies using Molecular field analysis (MFA), Regression analysis were carried out using GFA method. A highly predictive and statistically significant model was generated. The analyzed MFA model demonstrated a good fit, having r value of 0.927, cross-validated coefficient rCV value of 0.815 and rpred of 0.845.The QSAR models were found to accurately predict the Histone deacetylase2 inhibitory activity of structurally diverse test set compounds and to yield reliable clues for further optimization of the N(2-Aminophenyl)-Benzamide derivatives in the data set.